This invention relates to reducing cholesterol absorption from foods. Specifically, this invention provides a plant stanol food additive for reducing the absorption of cholesterol, a method of preparation, and a method of use of such a food additive.
Cholesterol has been known for many years to be a component of atherosclerotic plaques. Mounting evidence indicates diets high in cholesterol usually increase the levels of cholesterol in the blood which, in turn, increase risk of atherosclerotic disease with its attendant manifestations of heart attack, stroke and other tissue injuries resulting from atherosclerosis. Cholesterol absorbed from dietary sources is therefore thought to increase risk of atherosclerotic disease.
Based on a vast body of scientific evidence the National Institutes of Health (NIH) issued the following consensus statement which identified the risk factors for heart disease: "Lowering Blood Cholesterol to Prevent Heart Disease--Consensus Development Conference on Lowering Blood Cholesterol to Prevent Heart Disease", J. Am. Med. Assoc., 253, 2080-2086 (1985). NIH put forth a public warning against the consumption of foods with high cholesterol content. This recommendation, along with previous like statements by medical scientists and subsequent reinforcement in National Heart Lung and Blood Institute's "Report of the National Cholesterol Education Program, Expert Panel on Detection, Evaluation of Treatment of High Blood Cholesterol Levels in Adults", Arch. Int. Med. 148, 36-69 (1988), has led to a decrease in per capita consumption in the United States of high-cholesterol foods, especially meat and dairy products.
Other than avoidance or reduced consumption of high cholesterol foods, measures available without prescription to the general public to reduce the absorption of cholesterol from the diet have met with little success. Intake of dietary fibers for reducing cholesterol absorption requires large percentages of bulk fiber to be effective. For example, psyllium is required at from 5% to 30% by weight in cookies (U.S. Pat. No. 4,950,140, Pflaumer et al.). A formation of guar gum and calcium carbonate for therapeutic purposes to lower blood cholesterol requires 5 grams at each mealtime to be effective (U.S. Pat. No. 4,883,788, Day et al.).
The use of .beta.-sitosterol, a plant sterol, to reduce blood cholesterol has been known for a number of years. In 1953 Pollak reported the prevention of experimental atherosclerosis in rabbits by feeding a 6 to 1 ratio of sitosterol to cholesterol in feed. "Successful Prevention of Experimental Hypercholesterolemia and Cholesterol Atherosclerosis in the Rabbit", Pollak, O. J. Circulation, 7, 696-701 (1953). In 1956, Farquhar et al. reported significant reduction (17%) of serum cholesterol in young men with atherosclerotic heart disease. The dosage was 12-18 grams per day given in divided doses at mealtimes. "The Effect of Beta Sitosterol in Serum Lipids of Young Men with Arteriosclerotic Heart Disease", Farquhar, J. W., Smith, R. E., and Dempsey, M. E., Circulation 14 77-82 (1956).
Eli Lily marketed a sterol preparation from soybean oil, and later, from tall oil, called Cytellin.RTM.. In doses of 3 grams t.i.d. the soybean-derived Cytellin.RTM. lowered blood cholesterol by about 9% according to one report. "Effects of Plant Sterols on Cholesterol Metabolism in Man", Kucchodkar, B. J., Horlick, L., and Sodhi, H. S., Atherosclerosis, 23, 239-248 (1976). The tall oil-derived Cytellin.RTM. which was 93% .beta.-sitosterol, required dosages of from 3 to 18 grams per day to lower blood cholesterol by about 12%. "Plant Sterols as Cholesterol-Lowering Agents: Clinical Trials in Patients with Hypercholesterolemia and Studies of Sterol Balance", Lees, A. M., Mok, H. Y. I., Lees, R. S., McCluskey, M. A. and Grundy, S. M., Atherosclerosis, 28, 325-33 (1977). Other studies have substantiated the cholesterol lowering effect of sterols. "Response of Serum Lipids and Liproteins of Man to beta-sitosterol and Safflower Oil, A Long Term Study", Farquhar, J. W. and Sokolow, M., Circulation, 17, 890-899 (1958); and "Dietary Plant Sterols--Current Status in Human and Animal Sterol Metabolism", Subbisah, M. T. Ravi, Am. J. Clin. Nutr., 26, 219-225 (1973).
Thus, it is accepted that sterols in dosages of 3-18 grams per day can lower absorption of cholesterol from the gastro-intestinal tract and thereby reduce blood cholesterol.
In most of the above-mentioned studies the use of plant sterols is designed for the therapeutic use of lowering blood cholesterol in patients who have abnormally high blood cholesterol and are in need of treatment. Other preparations used for therapeutic effect include modified sterol molecules. See U.S. Pat. Nos. 4,602,003, Malinow, and 4,242,502, Malinow et al., which teach the synthesis and therapeutic use of saponins which are closely related to sterols. See also U.S. Pat. No. 4,117,121, Gallo-Jones, which discloses synthesis and use of another group of compounds which is closely related to sterols, 3.alpha., 12.alpha. dihydro cholanes, as therapeutic agents for lowering blood cholesterol levels.
Other research has demonstrated that stanols, the 5.alpha. saturated derivatives of plant sterols, are more effective as therapeutic agents in lowering blood cholesterol on a weight for weight basis than sterols. "Effect of Low-Dose Sitostanol on Serum Cholesterol in Patients with Hypercholesterole mia", Heinemann, T., Leiss, O. and von Bergamann, K., Atherosclerosis, 61, 219-223 (1986). This study demonstrated that 1.5 grams per day of a stanol mixture derived from soybean sterols was effective in lowering blood cholesterol by 15% after four weeks of therapy in patients with hypercholesterolemia, and suggested that low-dose sitostanol might be useful in therapy for patients afflicted with mild hypercholesterolemia.
In a comparison between sterols and stanols, equal amounts of sitostanol and sitosterol were infused into the gastro-intestinal (G.I.) tracts of human volunteers. Infusion of sterols resulted in a 50% reduction of cholesterol absorption while stanol infusion resulted in an 85% reduction in cholesterol absorption. "Comparison of Sitosterol and Sitostanol on Inhibition of Intestinal Cholesterol Absorption", Heinemann, T., Pietruck, B., Kullak-Ubilick, G., and von Bergmann, K., 4th Cologne Atherosclerosis Conference 1988, Birkhauser Verlag, Basel P. 117. The authors also measured absorption of the sterols and stanols. They found that there was a small but significant amount of sitosterol absorbed from the G.I. tract, but there was no measurable absorption of sitostanol under identical experimental conditions. These conclusions were verified by feeding studies of the two compounds in rats. "Comparison of Absorption and Metabolism of .beta.-Sitosterol and .beta.-Sitostanol in Rats", Ikeda I. and Sugano M., Atherosclerosis, 30, 227-237 (1978).
Stanols are more stable in heat and air than sterols because there are no unsaturated carbon-carbon bonds in stanols (U.S. Pat. No. 4,789,670, Tipton et al.).
Thus, stanols have three advantages over sterols for the inhibition of cholesterol absorption from the G.I. First, stanols are more effective by weight than sterols; second, stanols are absorbed from the G.I. tract to a lesser extent than sterols; and third, stanols are more chemically stable than sterols.
Stanols, in the above-mentioned report by Heinemann et al., are suggested as therapeutic agents directed toward treatment of mild hypercholesterolemia in specific patients in need of treatment. The instant invention is not intended for therapeutic purposes, but rather for use by the general public. The methods and composition of the instant invention comprise a food additive. Furthermore, the instant invention is intended for use in decreasing cholesterol absorption from only the food to which it is added.
Several compositions have been studied as food additives for the purpose of reducing cholesterol absorption from food products; they are described in contrast to the above-mentioned therapeutic which are used for lowering blood cholesterol level
A food product including sucrose polyesters and vegetable proteins as a substitute for foods high in cholesterol such as beef is disclosed in U.S. Pat. Nos. 4,789,664, Tipton et al. 4,034,083, Mattson, discloses a fat substitute including polyol fatty acid esters fortified with fat soluble vitamins as a method of reducing cholesterol absorption when used as a salad oil or cooking oil. "Optimizing the Effect of Plant Sterols on Cholesterol Absorption in Man", Mattson, F. H., Grundy, S. M., and Crouse, J. R., Am. J. Clin. Nutr. 35, 697-700 (1982) suggested the inclusion of sterols for food additives as well as for therapeutic agents. "Effect of Plant Sterols on Lipids and Atherosclerosis", Pollack, O. J., Pharmac. Ther., 31, 177-208 (1985) suggested the inclusion plant sterols such as .beta.-sitosterol in such foods as butter and margarine to "counteract not only the cholesterol in butter but all other dietary cholesterol and cholesterol from non-dietary sources available for absorption and re-absorption." In another study the ratio of about 2:1 (weight:weight) sterol to cholesterol was required to effect a 50% reduction in cholesterol absorption (e.g., from scrambled eggs), Mattson et al., supra (1982). Several patents also disclose uses of sterols in edible cooking oils for hypocholesterolemic effect (U.S. Pat. Nos. 3,865,939, Jandacek; 3,751,659, Erickson; and 3,085,939, Wruble et al.).
Conspicuously lacking in the above-identified literature is a food additive composition for reducing cholesterol absorption which is inexpensive, stable in storage, non-absorbable, and effective in small amounts to make it convenient for use.
Moreover, at this time the only widespread and safe method of reducing absorption of cholesterol from food products is actual avoidance of foods which contain cholesterol such as meats, eggs, and dairy products, thereby making maintenance of nutritious diets less convenient since meat, eggs, and dairy products are excellent sources of nutrition and staple foods of popular diets in many countries.
Furthermore, most pharmaceutical agents presently available for lowering blood cholesterol are relatively expensive and have side effects.